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Biomedical subjects

Y Zhao

Publications and source records attributed to Y Zhao.

At least 145 records · Page 8Linked to original sources
PubMed2001

Changes in response modulation of cat perigeniculate neurons related to EEG state and application of neuromodulators.

Spike activity of single perigeniculate (PGN) neurons was recorded in the anaesthetized (N2O/halothane) and paralysed cat during presentation of moving gratings of optimal spatial frequency. Typically, the ongoing (tonic, spontaneous) activity of PGN cells increased during a rise in EEG delta power accompanied by a reduction and often a total loss of spike rate modulation by the moving grating. The opposite behaviour was found when the EEG delta power vanished. Micro-iontophoretically applied acetylcholine (ACh) had an effect similar to a decrease in EEG delta power, decreasing ongoing activity but increasing the response modulation depth. The opposite effect could be achieved with the excitatory action of serotonin (5-HT), mimicking a strengthened EEG delta power. These data support previous data indicating that PGN neurons contribute to spatio-temporal tuning of subcortical visual activity in a state-dependent way.

Acetylcholine↗
PubMed2001

New method for high-performance liquid chromatographic separation and fluorescence detection of ginsenosides.

A novel pre-column derivatization method for the quantitative determination of ginsenosides by HPLC with fluorescence detection was established. The double bond at the C24-C25 position of ginsenoside was converted into an aldehyde group by means of ozonolysis. Then the aldehyde group reacts with FMOC-hydrazine forming the ginsenoside FMOC-hydrazone. The derivatized products were separated by RP-HPLC with gradient elution. The detection limits of ginsenosides Rg1 and Rb1 were 2.0 ng (about 2.5 pmol) and 1.0 ng (about 0.9 pmol), respectively. This method can be used for all ginsenosides having the C24-C25 double bond.

Chromatography, High Pressure Liquid↗
PubMed2001

Nipple fluid carcinoembryonic antigen and prostate-specific antigen in cancer-bearing and tumor-free breasts.

PURPOSE: Mammograms and breast examinations are established methods for early breast cancer detection. Routine mammography screening reduces breast cancer mortality among women ages > or = 50 years, but additional screening methods are needed. We and others have found high levels of carcinoembryonic antigen (CEA) and prostate-specific antigen (PSA) in nipple aspirate fluids (NAFs), but the usefulness for these bio-markers for early breast cancer detection is unknown. PATIENTS AND METHODS: NAFs from one or both breasts of 388 women were analyzed for CEA, PSA, and albumin levels. The study included 44 women with newly diagnosed invasive breast cancers, 67 women with proliferative breast lesions (ductal and lobular carcinoma in situ and atypical ductal hyperplasia), and 277 controls without these breast lesions. Analyses were conducted using the log(10)-transformed CEA and PSA levels to normalize the distributions of these tumor markers. RESULTS: Nipple fluid CEAs are significantly higher for cancerous breasts than tumor-free breasts (median 1,830 and 1,400 ng/mL, respectively; P <.01). However, at 90% specificity of the assay (CEA = 11,750 ng/mL), the corresponding sensitivity for cancer detection is 32%. CEA levels are not significantly different for breasts with proliferative lesions compared with tumor-free breasts. Nipple fluid PSAs do not differ by tumor status. Analyses of NAF albumin-standardized CEAs and PSAs yield similar results. Nipple fluid CEA and PSA titers are correlated in the affected and unaffected breast of women with unilateral lesions. CONCLUSION: Nipple fluid CEAs are higher for breasts with untreated invasive cancers, but the test sensitivity is low. Nipple fluid PSA titers do not seem to be useful for breast cancer detection.

Adult↗
PubMed2001

Proton-transfer reactions between nitroalkanes and hydroxide ion under non-steady-state conditions. Apparent and real kinetic isotope effects.

The kinetics of the proton-transfer reactions between 1-nitro-1-(4-nitrophenyl)ethane (NNPE(H(D))) and hydroxide ion in water/acetonitrile (50/50 vol %) were studied at temperatures ranging from 289 to 319 K. The equilibrium constants for the reactions are large under these conditions, ensuring that the back reaction is not significant. The extent of reaction/time profiles during the first half-lives are compared with theoretical data for the simple single-step mechanism and a 2-step mechanism involving initial donor/acceptor complex formation followed by unimolecular proton transfer and dissociation of ions. In all cases, the profiles for the reactions of both NNPE(H) and NNPE(D) deviate significantly from those expected for the simple single-step mechanism. Excellent fits of experimental data with theoretical data for the complex mechanism, in the pre-steady-state time period, were observed in all cases. At all base concentrations (0.5 to 5.0 mM) and at all temperatures the apparent kinetic isotope effects (KIE(app)) were observed to increase with increasing extent of reaction. Resolution of the kinetics into microscopic rate constants at 298 K resulted in a real kinetic isotope effect (KIE(real)) for the proton-transfer step equal to 22. Significant proton tunneling was further indicated by the temperature dependence of the rate constants for proton and deuteron transfers: KIE(real) ranging from 17 to 26, E(a)(D) -- E(a)(H) equal 2.8 kcal/mol, and A(D)/A(H) equal to 4.95.

Journal Article↗
PubMed2001

Structure--activity relationships of side-chain modified didemnins.

The synthesis and antitumor activity of a novel didemnin B analogue containing a psi[CH2NH] amide bond surrogate between N-Me-D-Leu7 and Pro8 are reported. The analogue shows activity (GI50 = 4 nM) comparable to that of didemnin B (GI50 = 13 nM) in the NCI-60 tumor cell screen. This result, along with new data from previously reported synthetic didemnin analogues, is discussed within the context of the side-chain SAR for didemnins.

Antineoplastic Agents↗
PubMed2001

Complexation of trivalent lanthanide cations by galactitol in the solid state. The crystal structure and an FT-IR study of 2NdCl3.galactitol.14H2O.

The crystal structure of 2NdCl3.galactitol.14H2O has been determined. The crystal system is triclinic, space group: -1, with unit-cell dimensions: a = 9.736(2), b = 10.396, c = 8.027 A; alpha = 108.05(3), beta = 92.68(3), gamma = 88.44(3) degrees, V= 771.6(3) A3, Z = 2. Each Nd atom is coordinated to nine oxygen atoms, three from the alditol and six from water molecules, with Nd-O distances from 2.461 to 2.552 A. The seventh water molecule is hydrogen-bonded by the hydroxyl hydrogen on O-1 (O-1-H-ll...O-10, 2.639 A). The FT-IR spectra of 2NdCl3.galactitol.14H2O and 2PrCl3.galactitol.14H2O are analogous, and show that Pr and Nd have the same coordination mode. The IR results are consistent with the crystal structures.

Carbohydrates↗
PubMed2001

Sugar interaction with metal ions. The crystal structure and Raman spectra study of SmCl3-galactitol complex.

The crystal structure of 2SmCl3.galactitol.14H2O has been determined. The crystal system is triclinic, space group: P-1. The unit cell dimensions: a = 9.683(2) A, b = 10.341(2) A, c = 7.990(2) A; alpha = 108.01(3) degrees, beta = 92.71(3) degrees, gamma = 88.42(3) degrees. Each Sm atom is coordinated to nine oxygen atoms, three from the alditol and six from water molecules, with Sm-O distance from 2.417 to 2.520 A. The seventh water molecule is hydrogen-bonded by the hydroxy hydrogen on O-3 (O(3)-H(13)...O(10), 2.635 A). After forming complexes the peaks have shifted and the relative intensities have changed in the IR and Raman spectra, which are corresponding to the changes in bond distances and bond angles of the structures. The IR and Raman spectra of Pr-, Nd- and Sm-galactitol complexes are similar, which show that the three metal ions have the same coordination mode.

Crystallography, X-Ray↗
PubMed2001

A role for flavin monooxygenase-like enzymes in auxin biosynthesis.

Although auxin is known to regulate many processes in plant development and has been studied for over a century, the mechanisms whereby plants produce it have remained elusive. Here we report the characterization of a dominant Arabidopsis mutant, yucca, which contains elevated levels of free auxin. YUCCA encodes a flavin monooxygenase-like enzyme and belongs to a family that includes at least nine other homologous Arabidopsis genes, a subset of which appears to have redundant functions. Results from tryptophan analog feeding experiments and biochemical assays indicate that YUCCA catalyzes hydroxylation of the amino group of tryptamine, a rate-limiting step in tryptophan-dependent auxin biosynthesis.

Alleles↗
PubMed2001

Three novel high performance affinity chromatographic media for the separation of antithrombin III from human plasma.

Novel monodisperse, non-porous, cross-linked poly (glycidyl methacrylate) beads (PGMA) were employed as the support for high performance affinity chromatography. Heparin was covalently attached to PGMA beads by three different coupling methods. Heparin-PGMA-I was prepared by directly coupling amino-groups of heparin with PGMA. Heparin-PGMA-II and III were prepared by the coupling of heparin to amino-PGMA, which was obtained by amination of PGMA. Heparin-PGMA-II was prepared by coupling the carboxyl groups of heparin to amino-PGMA by using water-soluble carbodiimide as coupling reagent, and heparin-PGMA-III was prepared by the reductive amination of heparin and amino-PGMA with sodium cyanoborohydride. The heparin contents of heparin-PGMA-I, II and III were 1.6, 10.2 and 1.0 mg/g beads, respectively. Their affinity capacities for antithrombin III were investigated. Their binding activity to antithrombin III was not proportional to the content of heparin immobilized, and heparin-PGMA-I was the most efficient affinity medium for antithrombin III. The resultant affinity media presented minimal non-specific interaction with other proteins and can be used in a wide pH range. All the three heparin-PGMA beads were exploited for the separation of antithrombin III from human plasma. The purity of antithrombin III obtained was higher than 90%, which was confirmed by high performance size exclusion chromatography.

Antithrombin III↗
PubMed2001

Allelic loss and gain, but not genomic instability, as the major somatic mutation in primary hepatocellular carcinoma.

To identify genetic abnormalities in primary hepatocellular carcinoma (HCC), we performed microsatellite analysis (MSA) on 60 Chinese HCC specimens. Utilizing a semi-quantitative MSA and 292 highly polymorphic markers spanning all 22 autosomes, we found that somatic allelic imbalance (AI) occurred frequently in HCC. To evaluate the nature of the AI, comparative genomic hybridization was performed on 20 HCC specimens. The combined use of these two methods revealed frequent allelic loss on 17p, 9p21-p23, 4q, 16q21-q23.3, 13q, 8p21-p23, and 6q24-q27, whereas there was frequent allelic gain on 1q, 17q, and 8q24. The region with the highest incidence of genomic imbalance was 17p13 (65%), followed by 9p21-p23 (55%), 4q (35-51%), 16q21-q23.3 (52%), 17p12 (49%), 13q (39-46%), 8p21-p23 (41-45%), 8q24 (41%), and 1q32 (40%). In addition, aberrations of 19p13.3, 16p13.3, 13q33-q34, 9q13-31, and 7q were reported for the first time. The presence of a close correlation of 17p13 deletion with abnormalities of some other loci implies that 17p13 could play a crucial role in oncogenesis. Interestingly, microsatellite instability was rarely seen in our patients, in contrast to that observed in European HCC samples.

Adult↗
PubMed2001

Rearrangement with formamide extrusion in the electrospray mass spectra of aminoacylbenzylamines.

Several aminoacylbenzylamines and their analogs were synthesized and analyzed by electrospray ionization mass spectrometry together with high-resolution and tandem mass spectrometric techniques. Fragment ions ([M + H - CH3NO](+)) were observed and attributed to a transfer of the benzyl group to the N-terminal amino group, leading to elimination of formamide. The proposed mechanism is supported by accurate mass measurements, and by experiments on deuterium labeling and variations of functional groups.

Amino Acids↗
PubMed2001

Varied ecological environment and fluorosis in Tibetan children in the nature reserve of Mount Qomolangma.

To determine the extent of brick tea consumption fluorosis in children living at elevations of 2000 and 4300 m, 519 children aged 8-15 years living in Xiege'er Town at 4300 m and Zhangmu Town at 2000 m were examined for dental fluorosis, their urinary fluoride concentration was determined, their dietary structure investigated, and the fluoride concentrations of various foods, freshwaters, soils, and fuels determined. Fifteen Tibetan families living in these two areas of the nature reserve of Mount Qomolangma were studied according to UNEP, FAO, and WHO guidelines for the study of dietary intake of chemical contaminants, Horowitz's classification and examination of dental fluorosis, and Dean's dental fluorosis index. The results demonstrated that dental fluorosis in Tibetan children living at an elevation of 2000 m was significantly lower than that of children at 4300 m (P<0.01). Higher elevation can worsen the extent of fluorosis, leading to retention of fluoride in tissues as a result of hypoxia, but fluorosis can also be associated with the deterioration of the ecological environment at high elevation and a low-level economy. Beverages and foods mixed with brick tea water are responsible for the dental fluorosis in the children.

Adolescent↗
PubMed2001

Molecular mimicry and antigen-specific T cell responses in multiple sclerosis and chronic CNS Lyme disease.

The concept of molecular mimicry provides and elegant framework as to how cross-reactivity between antigens from a foreign agent with self proteins may trigger autoimmune diseases. While it was previously thought that sequence and structural homology between foreign and self proteins or the sharing of T cell receptor (TCR) and MHC-binding motifs are required for molecular mimicry to occur, we have shown that even completely unrelated peptide sequences may lead to cross-recognition by T cells. The use of synthetic combinatorial peptide libraries in the positional scanning format (PS-SCL) together with novel biometric prediction approaches has allowed us to describe the recognition profiles of individual autoreactive T cell clones (TCC) with unprecedented accuracy. Through studies of myelin-specific TCC as well as clones from the nervous system of patients suffering from chronic central nervous (CNS) Lyme disease it has become clear that at least some T cells are more degenerate than previously anticipated. These data will not only help us to redefine what constitutes specific T cell recognition, but also allow us to study in more detail the biological role of molecular mimicry. A recent clinical trial with an altered peptide ligand (APL) of one of the candidate myelin basic protein (MBP) epitopes in MS (amino acids 83-99) has shown that such a modified MBP peptide may not only have therapeutic efficacy, but also bears the potential to exacerbate disease. Thus, we provide firm evidence that the basic principles of cross-recognition and their pathogenetic significance are relevant in MS.

Amino Acid Sequence↗
PubMed2001

Analysis of nuclear apoptotic process in a cell-free system.

We report an analysis of the apoptotic process of mouse liver nuclei induced in a cell-free carrot cytosol system by cytochrome c. Typical characteristics of apoptosis were observed, such as chromatin condensation, margination, apoptotic bodies and DNA ladders. Furthermore, transmission and scanning electron microscope analysis of the apoptotic nuclei detected chromatin-free nuclear vesicles before apoptotic bodies appeared at a comparatively late phase. When AC-YVAD-CHO, an inhibitor of caspase 6, was introduced into the system, these vesicles and apoptotic bodies disappeared completely within our study sections. We confirmed the results using whole-mount electron microscopy, and found that although the nuclear lamina was destroyed early, the nuclear matrix largely remained intact during the course of apoptosis. The nuclear matrix played an important role in maintaining the integrity of apoptotic cells and connecting the apoptotic bodies and apoptotic nucleus.

Animals↗
PubMed2001

A genome-wide search for type II diabetes susceptibility genes in Chinese Hans.

AIMS/HYPOTHESIS: The aim of the study was to search for Type II (non-insulin-dependent) diabetes mellitus susceptibility genes in a Chinese population. METHODS: A genome-wide scan was carried out using non-parametric linkage analyses. We studied 102 families (478 family members) who were Chinese Hans residing in east and south-east China, including 282 diabetic patients, among them 142 independent affected sibpairs were available for genotyping. A total of 247 fluorescence labelled microsatellite markers, with an average resolution of 15 cM, were amplified. GENEHUNTER was used for the non-parametric linkage analyses. RESULTS: Two loci on chromosome 9 D9S171 and D9S175 showed suggestive evidence for linkage, with an NPL-score of 3.286 and 2.939 respectively, and a p value of 1.19 x 10(-4) and 4.47 x 10(-4). A locus on the long arm of chromosome 20, D20S196 showed a rise in the non-parametric-linkage score (from 1.517 to 2.922) and a corresponding decrease in the p value from 0.04 to 6.5 x 10(-4) when families with lower BMI were analysed alone. Other loci with weaker evidence for linkage were also observed. CONCLUSIONS: Our results suggest that chromosome 9 contains genes involved in the susceptibility to Type II diabetes in an eastern and southeastern Chinese Han population, and chromosome 20 could hide genes linked to Type II diabetes in families with a lower BMI. Other regions could also hide susceptibility genes with minor effects.

Body Mass Index↗
PubMed2001

Spam1 (PH-20) mutations and sperm dysfunction in mice with the Rb(6.16) or Rb(6.15) translocation.

In mice bearing the Rb(6.16) or Rb(6.15) Robertsonian translocation (Rb), sperm dysfunction associated with the Rbs has been shown to lead to transmission ratio distortions (TRDs) in heterozygotes. The severity of the TRDs is directly related to the severity in the alteration of expression of the gene for the Sperm Adhesion Molecule 1 (Spam1), which maps to proximal mouse Chromosome 6 (Chr 6) near the translocation junction and encodes a sperm antigen with hyaluronidase activity. Here we demonstrate that there is a significantly reduced fertility in the Rb homozygotes (P < 0.001), based on litter size; and that with the Sperm Select Penetration assay Rb-bearing sperm have significantly decreased (P < 0.02-0.001) rates of penetration of hyaluronic acid. Catalytic kinetics studies indicate that reduced Spam1 (PH-20) hyaluronidase activity in the Rb(6.15) mice results from a qualitative defect, while for Rb(6.16) with the greater TRD both a qualitative and a quantitative deficiency (confirmed by Western analysis) of Spam1 exist. Six point mutations were shown to be clustered in the Spam1 hyaluronic acid-binding domain in Rb(6.15). For Rb(6.16) which has a gross genomic alteration at the Spam1 locus, 11 point mutations are scattered in the 5' and 3' UTRs and the coding region, where one leads to the replacement of a conserved residue. Entrapment of spontaneous Spam1 mutations, owing to recombination suppression near the Rb junctions, is proposed as the major underlying defect of the sperm dysfunction.

Animals↗
PubMed2001

Topoisomerase-I- and Alu-mediated genomic deletions of the APC gene in familial adenomatous polyposis.

Germline mutation in the adenomatous polyposis coli (APC) gene results in familial adenomatous polyposis (FAP), a heritable form of colorectal cancer. We have previously reported two novel mutations that delete exons 11 and 14 of the APC gene, respectively, at the cDNA level without any splice junction defects at the genomic level. We describe here the precise breakpoints of the two mutations and the possible mechanisms leading to the genomic rearrangement. The first rearrangement is most likely a topoisomerase-I-mediated non-homologous recombination resulting in a 2-kb deletion that deletes exon 11 of the APC gene. Both 5' and 3' breakpoints have two topoisomerase I recognition sites and runs of pyrimidines within the 10-bp sequences in their vicinity. Further, the 3' breakpoint has an adenine-thymidine-rich region. This is probably the first report of a topoisomerase-I-mediated germline mutation in a tumor suppressor gene. The second rearrangement is most likely an Alu-Alu homologous recombination resulting in a 6-kb deletion encompassing exon 14. The Alu elements at the 5' and 3' breakpoints include the 26-bp core sequence thought to stimulate recombination. In both rearrangements, partial sequences from the long interspersed nuclear element family are in the vicinity of the breakpoints. Other than serving as markers for regions of DNA damage, their precise role in the recombination events, if any, is unclear. Both deletions result in truncated APC proteins missing the beta-catenin- and axin-binding domains, resulting in severe polyposis and cancer.

Adenomatous Polyposis Coli↗